Can J Diabetes 41 (2017) 114–119

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Review

Effects of Diabetes Mellitus on Cognitive Decline in Patients with

Alzheimer Disease: A Systematic Review
Jun Li MD a,b,*, Matteo Cesari MD, PhD b, Fei Liu MD c, Birong Dong MD, PhD a, Bruno Vellas MD, PhD b
a The Center of Gerontology and Geriatrics, West China Medical School/West China Hospital, Sichuan University, Chengdu, Sichuan, China
b
Institut du Vieillissement, Gérontopôle, Université Toulouse III-Paul Sabatier, Toulouse, France
c
Department of Nephrology, West China Medical School/West China Hospital, Sichuan University, Chengdu, Sichuan,China

a r t i c l e i n f o a b s t r a c t

Article history: Basic and clinical research support a link between diabetes mellitus and Alzheimer disease (AD). However,
Received 7 December 2015
the relationship with AD progression is unclear. This review focuses on the association between diabe-
Received in revised form
tes and cognitive decline in patients with AD.
26 June 2016
Accepted 14 July 2016 The literature published through May 2015 was searched in 3 databases: PubMed, Embase and Cochrane.
Studies evaluating the effects of diabetes on patients with AD or cognitive decline were included, and
extracted data were analyzed. A total of 10 articles met the inclusion criteria for review. The results of
Keywords:
Alzheimer disease these studies were inconsistent in terms of the association between diabetes and cognitive decline. Only
cognitive decline 2 studies demonstrated that the presence of diabetes was independently related to the progression of
cognitive function cognitive decline in the patients with AD, and 3 studies suggested that histories of diabetes were not cor-
diabetes mellitus related with the changes in cognitive function in patients with AD. Half of the included studies even indi-
systematic review cated that histories of diabetes were associated with lesser declines in cognitive function in patients with
AD.
Current evidence indicates that the link between diabetes and cognitive decline in patients with AD
is uncertain. Further clinical studies are needed, with larger samples, long-term follow up and an extended
battery of cognitive assessments.
© 2016 Canadian Diabetes Association.

r é s u m é
Mots clés :
La recherche fondamentale et la recherche clinique établissent un lien entre le diabète sucré et la maladie
maladie d’Alzheimer
déclin cognitif
d’Alzheimer (MA). Cependant, la relation avec la progression de la MA n’est pas claire. La présente revue
fonctionnement cognitif porte sur l’association entre le diabète et le déclin cognitif chez les patients atteints de la MA.
diabète sucré La littérature publiée jusqu’en mai 2015 a été recherchée dans 3 banques de données : PubMed, Embase
examen systématique et Cochrane. Les études qui évaluent les effets du diabète sur les patients souffrant de la MA ou d’un déclin
cognitif ont été choisies, puis les données extraites ont été analysées. Un total de 10 articles répondaient
aux critères d’inclusion de la revue. Les résultats de ces études étaient contradictoires en fait d’association
entre le diabète et le déclin cognitif. Seules 2 études démontraient que la présence du diabète était
indépendamment liée à la progression du déclin cognitif chez les patients atteints de la MA, et 3 études
suggéraient que les antécédents de diabète n’étaient pas corrélés avec les changements dans le
fonctionnement cognitif des patients atteints de la MA. La moitié des études indiquaient même que les
antécédents de diabète étaient associés à un déclin moindre du fonctionnement cognitif des patients atteints
de la MA.
Les données probantes actuelles indiquent que le lien entre le diabète et le déclin cognitif chez les
patients atteints de la MA est incertain. D’autres études cliniques qui comportent des échantillons de plus
grande envergure, un suivi à long terme et une vaste batterie d’évaluations du fonctionnement cognitif
sont nécessaires.
© 2016 Canadian Diabetes Association.

* Address for correspondence: Jun Li, MD, The Center of Gerontology and Geriatrics, West China Medical School/West China Hospital, Sichuan University, No. 37, GuoXue
Xiang, Renmin Nan Lu, Chengdu, Sichuan 610041, China.
E-mail address: jundream2013@163.com (J. Li).

1499-2671 © 2016 Canadian Diabetes Association.

http://dx.doi.org/10.1016/j.jcjd.2016.07.003
 J. Li et al. / Can J Diabetes 41 (2017) 114–119
Introduction
Age-related conditions, dementia and type 2 diabetes mellitus
(diabetes) are characterized by increased incidence and preva-
lence with ageing and have become a major public health concern
all over the world. It is estimated that 35.6 million people world-
wide were living with dementia in 2010, and this number is pro-
jected nearly to double every 20 years. By 2040, the number of
people with dementia is predicted to be 81.1 million worldwide (1).
At the same time, dementia is the main cause of disability in older
adults, thus representing a relevant burden for individuals and
society as a whole. Alzheimer disease (AD) is the most common form
of dementia in the elderly, and current estimates suggest that it may
affect more than 24 million individuals around the world (2). On
the other hand, according to the International Diabetes Federa-
tion, diabetes affects at least 382 million people worldwide, and that
number is expected to reach 592 million by the year 2035 (3). This
increase is particularly evident in the population older than 65 years
of age. About 26% of patients over the age of 65 have diabetes (4).
Older adults with diabetes also are at greater risk than other older
adults for all types of dementia, including AD (5).
Mounting epidemiologic studies (6–8) and biologic evidence
(9–11) support a link between diabetes and AD. Diabetes is asso-
ciated with the development of cognitive impairment because of
its vascular and neurodegenerative effects. As the most common
neurodegenerative disorder, AD is characterized by the presence of
several pathologic hallmarks, including neuronal loss, formation of
senile plaques composed of extracellular deposits of amyloid beta
(Abeta) in the brain. Insulin resistance, 1 of the major components
of type 2 diabetes, is a known risk factor for AD (11). Insulin resis-
tance increases Abeta generation in the brain, although the exact
mechanism is unknown (9). Thus, AD and diabetes may share
common cellular and molecular mechanisms. However, some study
results are controversial (12–15). It remains uncertain whether
diabetes promotes the progression of cognitive decline once AD is
diagnosed.
The primary objective of this systematic review was to explore
the cognitive decline occurring in patients with AD in relationship
to the presence of diabetes.
Methods
Databases and searches
On May 20, 2015, a search without time-span limitation was
performed in 3 databases: PubMed, Ovid Embase and Cochrane
Central Register of Controlled Trials. According to the principles of
evidence-based clinical practice, the search strategies were based
on Patient, Intervention/Control, Outcome (PICO) with Medical
Subject Headings (MeSH) searching terms: dementia, Alzheimer’s
disease, diabetes mellitus, diabetes, hyperglycemia and cognitive
decline. The searches were limited to literature in English and con-
cerning humans. There was no restriction regarding the type of
publication or publication status. Additional manual searches were
also conducted in order to complete the reference list, starting with
the articles already identified.
Selection of studies
Search results were imported to Endnote, and duplicates were
removed. Two reviewers (JL, FL) independently checked the titles
and abstracts of articles for inclusion based on the following selec-
tion criteria. The full texts of the articles were retrieved if there was
any doubt whether the article should be excluded or not. Disagree-
ments were resolved by discussion, if necessary.
115
Inclusion criteria
To be included, articles had to meet the following 6 inclusion
criteria:
1) Original clinical study, independent of its study design;
2) Enrolment with AD at 18 years of age or older, regardless of
gender, disease course or disease severity;
3) Diagnosis of AD in agreement with any 1 of the following
operational definitions:
a) The International Classification of Diseases (ICD) v. 9 or
10 (ICD 1989; World Health Organization (WHO 1992);
b) The Diagnostic and Statistical Manual of Mental Disor-
ders (DSM) III, III-R, and IV (American Psychological Asso-
ciation (APA) 1980; APA 1987; APA 1994);
c) The National Institute of Neurological and Communica-
tive Disorders and Stroke and the Alzheimer’s Disease and
Related Disorders Association (NINCDS/ADRDA) (16);
4) Evaluation of the effect of diabetes on cognitive function in
patients with AD, independent of the type of diabetes;
5) If several vascular risk factors were simultaneously assessed
in a study of AD, the study was retained if it described the
specific effects of diabetes on cognition;
6) One or more cognitive tests were used to assess the cognitive
function modifications.
Any duration of follow up was eligible. If several papers from
the same cohort/study had been published, the most complete and
recent study was considered in the present review.
Exclusion criteria
Studies evaluating patients with dementia other than AD or
involving participants younger than 18 years of age were not con-
sidered in the present review.
Data extraction
Data were extracted independently by 2 reviewers (JL, FL)
from the included articles. Information on age and number of
participants, study design, severity of AD, outcome measures on
cognitive decline, duration and completeness of follow up, and con-
clusions drawn by authors were collected. The main limitations of
each study were identified as well as its main strengths. Disagree-
ments were resolved through discussion with a third member (BD)
of the review team, if necessary.
Results
A flowchart of the search is shown in the Figure 1. A total of 1249
potentially relevant articles were retrieved by the above-described
search strategy. Duplicate studies (n=223) and reviews (n=376) were
excluded. Based on title and abstract screening, 622 articles were
then excluded. After full-text evaluation, another 18 were found to
be off topic or irrelevant for the purpose of the present review.
The inclusion criteria were met by 10 articles that included a
total of 3162 patients (12–15,17–22). In other words, these patients
were diagnosed as having diabetes with AD. Of the included studies,
4 were conducted in the United States (12,14,17,18); other studies
were from Europe, Asia and South America (13,15,19–22). All of them
were cohort studies (6 prospective cohort studies and 4 retrospec-
tive cohort studies). The number of participants ranged from 101
to 972 subjects. The ages of the participants ranged from 70 to 84
years at the baseline visits. The follow-up times ranged from 12 to
60 months. Of the studies (12,14,15,18,20,22), 6 recruited partici-
pants in the community; the other 4 studies did not provide infor-
mation about the sources of the study populations.
116 J. Li et al. / Can J Diabetes 41 (2017) 114–119
PubMed Embase Cochrane
N = 927 N = 274 N = 48
-Duplicates deleted: N = 223
-Review: N = 376
Title/abstract screening
N = 650
Excluded: N = 622
-Not AD: N = 462
-Not diabetes: N = 92
-Not cognitive function: N = 18
-Not human: N = 50
Full text screening
N = 28
Excluded: N = 18
-Not AD: N = 7
-Not diabetes on the effect
of cognitive decline: N = 5
-Not cognitive function: N = 4
Included full text
N = 10
Figure 1. Flowchart of article selection process.
Nine studies (12–14,17–22) described the stages of the included
patients with AD. Only 1 study (20) included patients with severe
AD, whereas the other 8 recruited patients with mild or moderate
forms of the disease. Six studies (12,13,17–19,22) stated that the
duration of AD ranged from 3 months to 57.6 months. Most of the
studies adopted the Mini Mental State Examination (MMSE) to
measure the participants’ cognitive function and decline. Only
Helzner et al provided the results of a comprehensive battery of cog-
nitive tests (14).
Most of the included studies did not state the type of diabetes.
Almost all of the studies indicated that diabetes was considered
present if the participant was taking antidiabetic medications and/or
reported histories of diabetes at baseline. Only 1 study (13) used
the criteria of the ADA and WHO to define the diagnosis of diabe-
tes. Seven studies (14,15,18–22) described the prevalence of dia-
betes in the studied population to range from 10.4% to 33%. Only
1 study (13) reported the time since diabetes diagnoses.
All included studies are shown in the Table 1, with their char-
acteristics and their results. Because the included studies are dif-
ferent in outcome measurements and statistical analyses, it is
unsuitable to combine the results together quantitatively. Among
included studies, 5 studies (overall n=1970) indicated that patients
with AD and diabetes showed less cognitive decline than those
without the metabolic condition (12,13,18,19,22). Three studies
(overall n=621) reported no significant effects of diabetes on cog-
nitive decline (17,20,21). Only 2 studies (overall n=571) demon-
strated that patients with diabetes were more likely to decline in
cognitive function (14,15).
Discussion
Previous epidemiologic research has suggested that diabetes can
cause decline in cognitive function and can be associated with an
increased risk for AD (6–8). Therefore, at the beginning of these
included studies, researchers, without exception, hypothesized that
diabetes could cause faster decline in cognitive function in patients
with AD. However, only 2 of 10 included studies drew the expected
conclusion. More studies indicated that in patients with AD, the pres-
ence of diabetes was not related to the decline of cognitive func-
tion; some studies even suggested a protective role.
Why such heterogeneity of results and apparently contradic-
tive findings? Because the determinants of the accelerated cogni-
tive decline in patients with diabetes are less clear. The most studied
hypothesis suggests that the association may be the diabetic vas-
cular disease and inadequate cerebral circulation. What’s more,
hyperglycemia itself is a risk factor for cognitive dysfunction and
dementia. Recurrent hypoglycemic episodes have been suggested
to cause subclinical brain damage and permanent cognitive impair-
ment. Most recent studies have focused on the role of insulin and
insulin resistance as possible links between diabetes and AD (9,11).
Disturbances in insulin signalling in brain mechanisms may con-
tribute to the molecular, biochemical and histopathologic lesions
in patients with AD. Based on this knowledge, De la Monte has even
suggested that AD may be termed “type 3 diabetes” (23).
As far as our research was concerned, several differences could
be identified when we compared the 2 positive studies with the
other 8 that reported neutral or negative findings. Several differ-
ences could be identified. First, the positive studies tended to have
the longest follow ups of the included studies; i.e. 1 was 42 months
(14), and another 60 months long (15). In this review, most of the
included studies had ranges of follow up between 18 and 36 months.
Taking into account the natural progression of AD, the ages of
patients and the high rates of attrition, a longer follow up might
be important to describe and determine progression-related
differences (24).
Second, in the study of Helzner and colleagues (14), cognitive
change was measured through a comprehensive battery of cogni-
tive tests. The comprehensive battery assessed 5 cognitive domains
(including memory, abstract reasoning, visual spatial, language and
executive speed) using 12 different tests. All the other studies
assessed cognitive modifications only, basing their results on the
MMSE scores. The sensitivity of the MMSE as an assessment tool
to measure the cognitive changes of patients with diabetes is
debated, although it is the best-known paper-and-pencil test and
has been the most commonly used short screening tool for detect-
ing dementia since the 1970s (25). Diabetes is associated with cog-
nitive decline through several mechanisms and differing brain
pathologies. Under these circumstances, a multidomain test such
as the MMSE may be effective enough for use as a screening tool.
In a recent systematic review and meta-analysis, Tsoi and col-
leagues combined 102 studies that included 36,080 participants to
evaluate the diagnostic performance of the MMSE, and they dem-
onstrated that it is the most frequently studied test for dementia
screening (26). On the other hand, there are no agreements about
the best approach to registering the progression of dementia in
people with diabetes. It has been reported that the MMSE pres-
ents limited sensitivity in detecting the subtle effects of diabetes
on cognition compared with domain-specific neuropsychological
tests (27,28). Recently, a systematic review and meta-analysis by
Arevalo also showed the limitations related to the use of the MMSE
as a stand-alone single-administration test, especially in the domains
of language, praxis and executive functions (29). In addition, there
is also evidence that older adults with diabetes exhibit features of
impaired executive functions, which are dependent mostly on the
frontal lobes, even in the absence of significant cognitive impair-
ment when screened with the MMSE (30).
Third, it is noteworthy that there was a high prevalence of dia-
betes at the baseline in the study of Li and colleagues (15). In that
study, the prevalence of diabetes was 21.3% in the patients who com-
pleted follow up and 33% in those who did not. In the other studies,
the prevalence of diabetes ranged between 10% and 18%. The
 J. Li et al. / Can J Diabetes 41 (2017) 114–119 117

Table 1
Characteristics and results of all included studies

Author Study design Dementia diagnosis Diabetes diagnosis Cognitive Results

assessment

Diabetes associated with greater decline in AD

Helzner 2009 (14) Retrospective cohort Diagnostic criteria: Diagnostic criteria: history or A comprehensive The history of diabetes was
N=156 NINCDS-ADRDA antidiabetic medication use battery of associated with an additional
Age: 83 AD stage: mild at baseline, cognitive tests 0.05 SD decrease in cognitive
Follow up: 42 months Duration: not stated prevalence: 16% score per year (p=0.05)
Li 2010 (15) Prospective cohort Diagnostic criteria: Diagnostic criteria: history MMSE Mixed random effects regression
N=415 NINCDS-ADRDA, DSM-IV at baseline, model: after adjusting for
Age: 72~73 AD stage: not stated Prevalence: 21.3%-33% confounding factors, AD patients
Follow up: 60 months Duration: not stated with diabetes had faster
cognitive decline rates than the
subjects without such risk
factors (p<0.001).
No significant association
Bhargava 2006 (22) Retrospective cohort Diagnostic criteria: Diagnostic criteria: history MMSE, CDR Patients who progressed to the
N=247 NINCDS-ADRDA Prevalence: not stated moderate stage were designated
Age: 70.7~71.7 Stage: mild fast progressors; those who
Follow up: 36 months Duration: 42.5 months remained in the early stage were
designated slow progressors. The
history of diabetes did not differ
between groups (p=0.77).
Regan 2006 (21) Prospective cohort Diagnostic criteria: Diagnostic criteria: MMSE, SIB, Linear regression analysis: diabetes
N=224 NINCDS-ADRDA history ADAS-Cog did not significantly increase
Age: 81 Stage: mild (30%), moderate Prevalence: 12.1% deterioration of MMSE, ADAS-
Follow up: 18 months (40%), severe (30%) cog and SIB, at 18 months in
Duration: not stated people with Alzheimer disease.
Sakurai 2011 (17) Prospective cohort Diagnostic criteria: Diagnostic criteria: history of MMSE Multiple regression analysis: there
N=150 NINCDS-ADRDA diabetes or antidiabetic was no significant correlation of
Age: 78.6 Stage: mild and moderate Prevalence: 20% annual MMSE score changes
Follow up: 39 months Duration: not stated with diabetes in patients with
AD s (p=0.855).
Diabetes-associated less decline in AD
Ascher-Svanum Retrospective cohort Diagnostic criteria: Diagnostic criteria: history, MMSE, ADAS-Cog Compared with patients without
2015 (12) N=972 NINCDS-ADRDA, DSM-IV antidiabetic medication or diabetes, those with diabetes
Age: 74 Stage: mild and moderate random blood glucose showed a numerically but
Follow up: 18 months Duration: 48–51 months Prevalence: not stated statistically nonsignificantly
lesser cognitive decline (ADAS-
Cog score, 1.61 (p=0.21); MMSE
score, −0.40 (p=0.49)).
Dominguez 2012 Prospective cohort Diagnostic criteria: Diagnostic criteria: ADA/WHO MMSE, ADAS-Cog, Cognitive deterioration as reflected
(13) N=101 NINCDS-ADRDA, DSM-IV Prevalence: not stated CDR in the scores of MMSE and
Age: 76.3 Stage: mild and moderate ADAS-Cog score is statistically
Follow up: 12 months Duration: 57.6 months significantly lower in the AD
group with diabetes as
compared with pure demented
AD patients (p<0.05).
Musicco 2009 (19) Prospective cohort Diagnostic criteria: Diagnostic criteria: history of MMSE Multivariate hazard ratios:
N=154 NINCDS-ADRDA diabetes or antidiabetic diabetes were associated with
Age: 73 Stage: mild and moderate medication slower disease progression in
Follow up: 23 months Duration: 26 months Prevalence: 14.4% patients with AD. Patients with
diabetes had a 65% reduced risk
for cognitive decline compared
with patients with AD without
diabetes.
Sanz 2009 (18) Retrospective cohort Diagnostic criteria: Diagnostic criteria: history of MMSE Linear mixed model: the presence
N=608 NINCDS-ADRDA, MMSE diabetes or antidiabetic of diabetes was associated with a
Age: 76–78 Stage: mild and moderate medication lower rate of cognitive decline in
Follow up: 26 months Duration: 3.1–20.8 months Prevalence: 10.4% patients with AD (p=0.01).
Mielke 2007 (20) Prospective cohort Diagnostic criteria: Diagnostic criteria: self-report MMSE, CDR Linear mixed model: a history of
N=135 NINCDS-ADRDA Prevalence: 18.5% diabetes was associated with a
Age: 84 Stage: mild slower rate of cognitive decline
Follow up: 36 months Duration: 25 months (p<0.001).
ADA, American Diabetes Association; ADAS-Cog, Alzheimer’s Disease Assessment Scale-Cognitive Subscale; CDR, Clinical Dementia Rating; DSM, Diagnostic and Statistical
Manual of Mental Disorders; MMSE, Mini Mental State Examination; NINCDS-ADRDA, National Institute of Neurological and Communicative Disorders and Stroke and the
Alzheimer’s Disease and Related Disorders Association; SIB, severe impairment battery; WHO, World Health Organization.

diagnosis of diabetes was made on the basis of self-reported medical
histories or antidiabetic medications in almost all the included
studies. However, the latest report has showed that the percent-
age of patients over the age of 65 with diabetes is 26% or so (4).
Therefore, the accuracy of the diagnosis might be arguable. In par-
ticular, it has been reported in the literature that up to 12% of patients
with diabetes are not aware of their metabolic condition (31).
Underestimation and inaccurate diagnosis might thus introduce a
relevant misclassification bias potentially affecting the reported
findings.
Besides the above-mentioned issues, other possible explana-
tions might be provided for the uncertain results obtained. Long
follow-up durations were always accompanied by high drop-out
rates. Among the included studies, Li et al (15) reported that only
118 J. Li et al. / Can J Diabetes 41 (2017) 114–119
78% of participants completed the follow up. In the study by Helzner
et al (14), 34% patients died or were lost to follow up or refused to
complete the study. Mielke et al (18) had a drop-out rate of 37.5%
at the first follow-up visit. Sanz et al (22) stated that they experi-
enced a constant rate of attrition of 12% every 6 months. This kind
of survival bias might also contribute to the heterogeneous results.
In most of the included studies, the diagnostic processes of
diagnosing AD did not include neuroimaging and were not
neuropathologically confirmed. Only 3 studies indicated that par-
ticipants received neuroimaging examination (CT or MRI) to exclude
vascular dementia (13,19,21). Previous studies using imaging exami-
nations and neuropathologic data show that mixed dementia (AD
plus vascular dementia) is the most common cause of dementia,
even in the oldest (32). Therefore, it is likely that some of the par-
ticipants with AD actually had mixed dementia, with consequent
influence on the obtained results.
In the included studies, some detailed information on diabetes
was lacking, such as the times from the diabetes diagnoses, the times
of use of antidiabetic medications, the glycemic control condi-
tions and the patients’ weights and diets. These factors are all highly
relevant to the present analyses and may potentially influence the
relationship between diabetes and cognitive decline.
Some evidence has suggested that diabetes is associated with
less cognitive decline. In 1997 and 2005, 2 autopsy studies found
that patients with diabetes had no more neuritic plaques and neu-
rofibrillary tangles than those without diabetes (33,34). Besides,
Vlassara et al found that more than one-third of patients with AD
exhibited vascular and microvascular pathology and/or degenera-
tion (35), so it is possible that cognitive impairment in older persons
with diabetes might be due to the effects of cerebral microvascu-
lature pathology and its interaction with neuritic plaques and neu-
rofibrillary tangles (33). The group with diabetes may have more
vascular pathology, contributing to the initial diagnosis and sever-
ity of dementia but to a lower burden of AD pathology. This may
potentially lead to a protective effect of diabetes on cognitive decline
in individuals with AD.
Another possible explanation for the unusual relationship is the
use of antidiabetic medications. It is widely accepted that treat-
ment is an important factor that may influence the progression of
AD (36). Sulfonylureas (independently, if alone, or in combination
with metformin) could reduce the risk for dementia (37,38). As the
most commonly used hypoglycemic drug, metformin prevented the
appearance of the molecular and pathologic characteristics observed
in AD (39,40) and decreased the risk for dementia (38). Glucagon-
like peptide-1 analogues are found to reduce plaque loads in murine
models and, when tested in patients with AD, to reverse memory
impairment temporarily (41,42). Administration of pioglitazone could
significantly improve spatial cognition and learning and memory
performance and could decrease hippocampal hyperphosphorylated
tau protein and hippocampal galanin (43). Intranasal insulin use has
also been reported to delay cognitive decline in murine models (44)
and to preserve cognitive function in adults with mild AD (45). Fur-
thermore, it should not be ignored that elderly patients with dia-
betes may have more frequently received other cardiovascular
medications (i.e. antihypertensive drugs, low-dose aspirin or a statin)
than nondiabetic counterparts. For example, antihypertensive medi-
cations have been reported to decrease the risk of AD onset (46).
Some epidemiologic studies have found that statin or aspirin was
related to a lower risk for AD (47–49). Overall, a more aggressive
treatment of nonneurodegenerative conditions minimizing cogni-
tive function might explain why patients with diabetes present lower
rates of decline compared to their counterparts.
In summary, we did not find evidence supporting the link
between diabetes and cognitive decline in patients with AD after
an extensive search and analysis of available information. Future
trials are required to clarify the link and to address the question
of whether cognitive decline may be prevented or slowed by
adequate metabolic control.
Conclusions
Based on current evidence, the causative relationship between
diabetes and cognitive decline in patients with AD has not yet been
clearly established. To date, no intervention has yet been identi-
fied for treating AD. Identifying independent predictors of AD will
help clinicians to estimate the disease’s prognosis and improve
patients’ care. It is clear that more extensive experimental and
clinical studies are needed, with larger sample sizes, longer follow-
ups and extended cognitive assessments in order to clarify the effect
of diabetes on cognitive function in patients with AD.
Acknowledgements
The work was supported by the National Natural Science
Foundation of China (grant #81371528 and #81300260); the
Sichuan Provincial Foundation of Science and Technology (Grant
#2013SZ0047 and 2014SZ0044) and International Visiting Program
for Excellent Young Scholars of Sichuan University.
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